The objective of this proposal is to continue the elucidation of the interacting control mechanisms operative between monoamines and amino acid metabolism which may involve the metabolism of the Krebs cycles associated with these amino acids. In vivo and in vitro studies of rat brain treated with drugs which affect catecholamines, (e.g., amphetamine, FLA-63) are proposed. Nigrl lesions will be prepared by stereotaxic injection of 6-OH dopamine. Doubling-labeling experiments with l4C-glucose and 3H-acetate will be utilized to follow the turnover rate of glutamate, glutamine, aspartate, GABA and the Krebs cycle. Discrete areas such as cerebral cortex, cerebellum, brain stem and caudate nucleus wil be studied. The effect of inhibitors of amino acid metabolism (e.g., alpha-fluoroglutarate, dipropyl acetic acid, aminooxyacetic acid) or of GABA transmission (bicuculline) on formation of catecholamine from 3H-tyrosine will be investigated in tissue slices and synaptosomal preparations. Correlations will be made of the turnover rates and levels of amino acids and monoamines.